A bioprinted and scalable model of human tubulo-interstitial kidney fibrosis.

Chronic kidney disease (CKD) affects more than 10% of the global population. As kidney function negatively correlates with the presence of interstitial fibrosis, the development of new anti-fibrotic therapies holds promise to stabilize functional decline in CKD patients. The goal of the study was to generate a scalable bioprinted 3-dimensional kidney tubulo-interstitial disease model of kidney fibrosis.

Thermally Assisted Microfluidics to Produce Chemically Equivalent Microgels with Tunable Network Morphologies.

Although micron-sized microgels have become important building blocks in regenerative materials, offering decisive interactions with living matter, their chemical composition mostly significantly varies when their network morphology is tuned. Since cell behavior is simultaneously affected by the physical, chemical, and structural properties of the gel network, microgels with variable morphology but chemical equivalence are of interest. This work describes a new method to produce thermoresponsive microgels with defined mechanical properties, surface morphologies, and volume phase transition temperatures.

Varying the Stiffness and Diffusivity of Rod-Shaped Microgels Independently through Their Molecular Building Blocks.

Microgels are water-swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method-all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications.

Cell Guiding Multicomponent Nanoyarn Tendon Scaffolds with Tunable Morphology and Flexibility.

Nanofibrous scaffolds are widely investigated for tendon tissue engineering due to their porous structure, high flexibility, and the ability to guide cells in a preferred direction. Previous research has shown that providing a microenvironment similar to in vivo settings improves tissue regeneration. Therefore, in this work, ingenious multicomponent nanoyarn scaffolds that mimic the fibrillar and tubular structures of tendons are developed for the first time through electrospinning and bundling nanoyarns followed by electrospinning of a nanofibrous shell around the bundle.

Liposome manufacturing under continuous flow conditions: towards a fully integrated set-up with in-line control of critical quality attributes.

Continuous flow manufacturing (CFM) has shown remarkable advantages in the industrial-scale production of drug-loaded nanomedicines, including mRNA-based COVID-19 vaccines. Thus far, CFM research in nanomedicine has mainly focused on the initial particle formation step, while post-formation production steps are hardly ever integrated. The opportunity to implement in-line quality control of critical quality attributes merits closer investigation.

Controlling Structure with Injectable Biomaterials to Better Mimic Tissue Heterogeneity and Anisotropy.

Tissue regeneration of sensitive tissues calls for injectable scaffolds, which are minimally invasive and offer minimal damage to the native tissues. However, most of these systems are inherently isotropic and do not mimic the complex hierarchically ordered nature of the native extracellular matrices. This review focuses on the different approaches developed in the past decade to bring in some form of anisotropy to the conventional injectable tissue regenerative matrices.

Bicyclic RGD peptides enhance nerve growth in synthetic PEG-based Anisogels.

Nerve regeneration scaffolds often consist of soft hydrogels modified with extracellular matrix (ECM) proteins or fragments, as well as linear and cyclic peptides. One of the commonly used integrin-mediated cell adhesive peptide sequences is Arg-Gly-Asp (RGD). Despite its straightforward coupling mechanisms to artificial extracellular matrix (aECM) constructs, linear RGD peptides suffer from low stability towards degradation and lack integrin selectivity.

How Much Physical Guidance is Needed to Orient Growing Axons in 3D Hydrogels?

Directing cells is essential to organize multi-cellular organisms that are built up from subunits executing specific tasks. This guidance requires a precisely controlled symphony of biochemical, mechanical, and structural signals. While many guiding mechanisms focus on 2D structural patterns or 3D biochemical gradients, injectable material platforms that elucidate how cellular processes are triggered by defined 3D physical guiding cues are still lacking but crucial for the repair of soft tissues.

Granular Cellulose Nanofibril Hydrogel Scaffolds for 3D Cell Cultivation.

The replacement of diseased and damaged organs remains an challenge in modern medicine. However, through the use of tissue engineering techniques, it may soon be possible to (re)generate tissues and organs using artificial scaffolds. For example, hydrogel networks made from hydrophilic precursor solutions can replicate many properties found in the natural extracellular matrix (ECM) but often lack the dynamic nature of the ECM, as many covalently crosslinked hydrogels possess elastic and static networks with nanoscale pores hindering cell migration without being degradable.

Hierarchical fibrous guiding cues at different scales influence linear neurite extension.

Surface topographies at micro- and nanoscales can influence different cellular behavior, such as their growth rate and directionality. While different techniques have been established to fabricate 2-dimensional flat substrates with nano- and microscale topographies, most of them are prone to high costs and long preparation times. The 2.

High-Throughput Production of Micrometer Sized Double Emulsions and Microgel Capsules in Parallelized 3D Printed Microfluidic Devices.

Double emulsions are useful geometries as templates for core-shell particles, hollow sphere capsules, and for the production of biomedical delivery vehicles. In microfluidics, two approaches are currently being pursued for the preparation of microfluidic double emulsion devices. The first approach utilizes soft lithography, where many identical double-flow-focusing channel geometries are produced in a hydrophobic silicone matrix.

Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension.

An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanical and biochemical properties were optimized. A recombinant fibronectin fragment (FNIII9*-10/12-14) was coupled to the PEG backbone during gelation to provide cell adhesive and growth factor binding domains in close vicinity.

Solvent-Induced Nanotopographies of Single Microfibers Regulate Cell Mechanotransduction.

The extracellular matrix (ECM) is a dynamic three-dimensional (3D) fibrous network, surrounding all cells in vivo. Fiber manufacturing techniques are employed to mimic the ECM but still lack the knowledge and methodology to produce single fibers approximating cell size with different surface topographies to study cell-material interactions. Using solvent-assisted spinning (SAS), the potential to continuously produce single microscale fibers with unlimited length, precise diameter, and specific surface topographies was demonstrated.

An Injectable Hybrid Hydrogel with Oriented Short Fibers Induces Unidirectional Growth of Functional Nerve Cells.

To regenerate soft aligned tissues in living organisms, low invasive biomaterials are required to create 3D microenvironments with a structural complexity to mimic the tissue's native architecture. Here, a tunable injectable hydrogel is reported, which allows precise engineering of the construct's anisotropy in situ. This material is defined as an Anisogel, representing a new type of tissue regenerative therapy.